morƒormance, llc is strategically positioned to address issues of the biological performance of individual and combination pharmaceutical agents. While the company’s technology platform for modifying the solid state form of pharmaceutical compounds can be applied to virtually any compound, our early focus has been with compounds in the cholesterol lowering drug category.
By producing more soluble and, thus, predictably more absorbable and bioavailable new forms of these compounds, these proprietary new forms can extend current product life, improve product performance, and preserve and expand markets for the compounds thus modified.
THE PRODUCTS
morƒormance has worked with aspirin to produce compelling proof of concept. Aspirin, the first blockbuster drug, was patented in 1900 and has only been available at room temperature in its characteristic crystalline Form I. The thermodynamics of this compound, with a transition glass temperature of minus 30 degrees Centigrade strongly favor crystallization at room temperature into Form I.
Through the morƒormance method, it has been possible to produce aspirin as a highly amorphous glass that has remained stable at room temperature for over two years. This result has never been achieved before.
morƒormance has focused on cholesterol lowering agents to produce highly amorphous glass forms of the major market statins – atorvastatin free acid, atorvastatin calcium, simvastatin, and rosuvastatin. morƒormance has produced compounds with higher degrees of flattening of the broad bands of absorption (measured by Fourier Transform Infrared Spectroscopy (FTIR) and the shortest degrees of local ordering ever demonstrated (measured by X-ray powder diffraction - XRPD).
A non-crystalline or amorphous compound refers to a compound that, upon a PXRD analysis, provides a pattern that is substantially free of any peak reflections that are typical of the crystalline form.
In an FTIR spectrograph a non-crystalline form will show broader absorption bands than its crystalline counterpart. A comparison between amorphous and crystalline FTIR spectra can confirm that the samples are from the same chemical entity.
Reduced local ordering translates into higher free energy and greater aqueous solubility. Compared to the crystalline form of a compound, the amorphous form (for a similar particle size) will usually have a 2-8 fold increase in solubility. For compounds of relatively poor aqueous solubility such as statins, this may translate to a direct 2-8 fold increase in bioavailability.
The cholesterol lowering agent ezetimibe has also been modified through this method. Not only has a highly amorphous glass form of ezetimibe been produced, a new crystal form distinctly different from the original crystalline material in its pattern of XRPD peaks has also been generated. Thus, this platform not only produces highly amorphous solid states, it also can be used to generate novel crystalline forms of a compound with the unique physical and chemical properties that attend a new crystal form.
Perhaps the most profound innovation of the morƒormance method is the ability to combine two or more compounds into highly interdispersed coamorphous states. As the only company capable of producing room temperature stable amorphous glass aspirin, an invention has been achieved that could reshape the cholesterol lowering market and, even more importantly, reshape the approach for optimizing pharmacodynamics of compounds. To each of the statins, aspirin has been added in a high molar ratio to yield a highly amorphous coamorphous combination of compounds. The much higher solubility of aspirin compared to the statins provides an unprecedented accelerated delivery method combined with the cardiovascular benefits of low dose aspirin.
THE PROPRIETARY CHEMISTRY TECHNOLOGY
morƒormance has developed a proprietary technology for the modification of the solid state form of pharmaceutical compounds. As a new tool not otherwise available, it provides a means of structural and functional modification beyond existing methods.
A new polymorphic form of a compound, either crystalline or amorphous, is currently interpreted as a new chemical entity (NCE). Therefore the new forms produced uniquely through the morƒormance method not only can improve compound performance, but can help preserve and expand market share.
The technology platform is based upon an innovation in laser technology that may increase the efficiency of a process known as photoacoustic resonance. This method allows the stimulation of specific vibrational modes within molecules to alter regional or backbone free energies and thus alter the form, function, and chemical reactivity of a molecule. Intermolecular resonances can also be stimulated altering the tendencies of the molecules to align in particular geometries in a crystal lattice, or for the orientations to randomize fully to produce a highly amorphous solid state.
The significance of this technology is that it results in 1) the ability to produce novel and patentable crystal forms of a compound not achievable through other methods, 2) generation of amorphous forms with extremely short local ordering for the highest possible aqueous solubility, 3) directed engineering of intra- and intermolecular ordering of molecules to improve the compound performance for the intended purpose.
Many promising compounds fail to make it to Phase I clinical studies because of solubility and bioavailability issues, and other compounds fail in Phase II or Phase III due to performance limitations. The morƒormance method provides a process of enhancing compound performance to obtain the greatest potential value and benefit for each compound.
Attributes of this method include:
Energy Requirements: Applying select frequencies to achieve resonance effects allows the use of appropriately powered wavelengths of laser light. This innovative technique reduces the likelihood of compound degradation during processing.
Nontoxic Solvents: The solvents used to apply this process have been water and ethanol, free of issues of residual solvent or environmental toxicity.
Flexibility: The method, employing quantum chemistry modeling, can focus an effect at a particular bond, at a group of bonds or region in a molecule, at the overall molecular backbone structure, or at the level of intermolecular interactions.
Compound Salvage: The method can be used to produce solid state forms of higher solubility or other enhanced performance attributes that elevate a failed compound to a clinically and commercially viable one.
Combinations of Compounds: New combinations of compounds that orchestrate additive or synergistic benefits for a particular purpose can be formulated in solid states of exceptional solubility and bioavailability.
The morƒormance method and the products delevoped via the method have issued patent, pending patent, and trade secret IP protection.
THE OPPORTUNITY
morƒormance is focused on producing novel compound forms of the highest performance possible as defined by efficiency of drug delivery to the target, the optimum intended biological response, and minimization of side effects. The morƒormance method can be applied to currently marketed compounds or to those in development so that a given compound can deliver the greatest biological benefits.
To accelerate development and broaden the company’s collaborative pipeline, morƒormance intends to partner or offer licensing. A strategic partner or licensee can benefit in a number of ways; these include:
1. Outlicensing of current morƒormance products including amorphous aspirin, amorphous statins, amorphous ezetimibe, and the co-amorphous and tri-amorphous combinations thereof.
2. Collaborative development of a novel morƒormance solid state product—providing enhancement of existing compounds or salvage of drug candidates abandoned due to safety or performance limitations due to low bioavailability.
3. Identification and selection of an indication and drug with the partner and subsequent development of an optimized form for drug delivery.
morƒormance will also consider capitalization opportunities through traditional venture organizations, philanthropic venture organizations and industry alliances.
Contact: Darrell Laham, Ph.D. Chief Executive Officer
Darrell@laham.net (303) 875-9045
4945 Eldorado Springs Drive, Boulder, CO 80303
Copyright © 2008 morƒormance, llc All rights reserved.
This information is intended only for business development units and executives of qualified pharmaceutical and biotechnology companies. morƒormance, llc does not offer any products to the general public. None of the above statements have been evaluated by the FDA.
morƒormance, llc is a privately held Colorado (USA) Limited Liability Company managed by its members. Additional membership opportunities are not available at this time.
The morƒormance method is protected by US and international patents. Other patents pending.
